Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial.

BACKGROUND: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. OBJECTIVE: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. DESIGN: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). SETTING: 23 hospitals in Norway. PATIENTS: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. INTERVENTION: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). MEASUREMENTS: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. RESULTS: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. LIMITATION: The trial had no placebo group. CONCLUSION: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19. PRIMARY FUNDING SOURCE: National Clinical Therapy Research in the Specialist Health Services, Norway.

Omicron Variant Generates a Higher and More Sustained Viral Load in Nasopharynx and Saliva Than the Delta Variant of SARS-CoV-2.

The Omicron variant of SARS-CoV-2 spreads more easily than earlier variants, possibly as a result of a higher viral load in the upper respiratory tract and oral cavity. Hence, we investigated whether the Omicron variant generates a higher viral load than that of the Delta variant in saliva and nasopharynx. Both specimens were collected from 52 Omicron and 17 Delta cases at two time points one week apart and analyzed by qRT-PCR. Viral load was measured as 10 log RNA genome copies per 1000 human cells according to the WHO reference standard. We found that Omicron cases carried a higher viral load and had more sustained viral shedding compared to the Delta cases, especially in the nasopharynx.

Breakthrough infections with the omicron and delta variants of SARS-CoV-2 result in similar re-activation of vaccine-induced immunity.

Background: Results showing that sera from double vaccinated individuals have minimal neutralizing activity against Omicron have been interpreted as indicating the need for a third vaccine dose for protection. However, there is little information about early immune responses to Omicron infection in double vaccinated individuals. Methods: We measured inflammatory mediators, antibodies to the SARS-CoV-2 spike and nucleocapsid proteins, and spike peptide-induced release of interferon gamma in whole blood in 51 double-vaccinated individuals infected with Omicron, in 14 infected with Delta, and in 18 healthy controls. The median time points for the first and second samples were 7 and 14 days after symptom onset, respectively. Findings: Infection with Omicron or Delta led to a rapid and similar increase in antibodies to the receptor-binding domain (RBD) of Omicron protein and spike peptide-induced interferon gamma in whole blood. Both the Omicron- and the Delta-infected patients had a mild and transient increase in inflammatory parameters. Interpretation: The results suggest that two vaccine doses are sufficient to mount a rapid and potent immune response upon infection in healthy individuals of with the Omicron variant. Funding: The study was funded by the Oslo University Hospital, and by grants from The Coalition for Epidemic Preparedness Innovations, Research Council of Norway (no 312780, 324272), South-Eastern Norway Regional Health Authority (no 2019067, 2021071, 10357, 2021047, 33612, 2021087, 2017092), EU Horizon 2020 grant no 848099, a philantropic donation from Vivaldi Invest A/S, and The European Virus Archive Global.

Multicenter Evaluation of Rapid BACpro® II for the Accurate Identification of Microorganisms Directly from Blood Cultures Using MALDI-TOF MS.

The identification of microorganisms directly from blood cultures using MALDI-TOF MS has been shown to be the most impacting application of this methodology. In this study, a novel commercial method was evaluated in four clinical microbiology laboratories. Positive blood culture samples (n = 801) were processed using a rapid BACpro® II kit and then compared with the routine gold standard. A subset of monomicrobial BCs (n = 560) were analyzed in parallel with a Sepsityper® Kit (Bruker Daltonics, Bremen, Germany) and compared with the rapid BACpro® II kit. In addition, this kit was also compared with two different in-house methods. Overall, 80.0% of the monomicrobial isolates (609/761; 95% CI 71.5-88.5) were correctly identified by the rapid BACpro® II kit at the species level (92.3% of the Gram negative and 72.4% of the Gram positive bacteria). The comparison with the Sepsityper® Kit showed that the rapid BACpro® II kit generated higher rates of correct species-level identification for all categories (p > 0.0001), except for yeasts identified with score values > 1.7. It also proved superior to the ammonium chloride method (p > 0.0001), but the differential centrifugation method allowed for higher rates of correct identification for Gram negative bacteria (p > 0.1). The percentage of accurate species-level identification of Gram positive bacteria was particularly noteworthy in comparison with other commercial and in-house methods.

Using 4+ to grade near-normal muscle strength does not improve agreement.

BACKGROUND: Manual assessment of muscle strength is often graded using the ordinal Medical Research Council (MRC) scale. The scale has a number of inherent weaknesses, including poorly defined limits between grades '4' and '5' and very large differences in the span of muscle strength encompassed by each of the six grades. It is not necessarily obvious how to convert a manual muscle test finding into an MRC grade. Several modifications which include intermediate grades have been suggested to improve the MRC scale and the current study examines whether agreement improves and variation in ratings decrease, with an intermediate grade between '4' and '5', in circumstances where such a grade would seem appropriate. The present study examined the hypothesis, that a modified MRC-scale which included the commonly used '4+' option, resulted in greater agreement between clinicians compared to the standard MRC-scale. METHOD: A questionnaire containing five simple clinical cases were distributed to a large convenience sample of chiropractors in Northern Europe, with instructions to grade the described muscle strength findings using the MRC scale. The scale was adapted (with/without an intermediate '4+' grade) depending on the preference of the individual respondent. The cases were designed in such a way as to suggest a muscle weakness in the grey area between '4' and '5', i.e. grade '4+' on the modified MRC scale. RESULTS: A total of 225 questionnaires were returned (7% response rate). The average percentage agreement (across cases) in the standard MRC group was 64% [range 51%: 73%] (grade '4' in all cases). In the modified MRC group, the corresponding findings was 48% [38%: 74%] (grade '4' or '4+' in all cases). The mean average deviation analogue in the standard MRC group was 0.34 (range 0.34: 0.40), compared to 0.51 (range 0.39: 0.73) in the modified MRC group, indicating greater dispersion of scores in the modified MRC group. The Fleiss kappa was 0.02 (p < 0.001) and 0.13 (p < 0.001), respectively. CONCLUSIONS: Contrary to the original hypothesis, introduction of a '4+' grade did not clearly improve agreement or variability of ratings, despite eliminating the physical muscle testing by providing written descriptions of test findings and specifically designing these to suggest a weakness of grade '4+'.

Verbal memory performance of mildly to moderately depressed outpatient younger adults.

BACKGROUND: Memory impairment is associated with major depression. Studies on young adults are, however, rare and show inconsistent and contradictory results. The present study investigated the relationship between mild to moderate depression and verbal memory functioning in a relatively large sample of young, non-psychotic, mainly non-medicated outpatients. METHODS: Fifty-seven clinically depressed were compared to 42 previously depressed and 46 never depressed controls on the California Verbal Learning Test. RESULTS: No difference in verbal memory functioning appeared between the three groups, and no difference were obtained between first-episode depressed individuals and individuals with recurrent depression. LIMITATIONS: The study was cross-sectional and prospective studies are needed to confirm our findings. CONCLUSIONS: Our results suggest that relatively young, non-medicated outpatients with mild to moderate depression are not affected by verbal memory impairments.